There are challenges in developing and evaluating new pharmacological and non-pharmacological therapies in Palliative Care. The pathophysiology of many of the symptoms faced at the end of life remain poorly understood, and may vary between disease processes (e.g. dyspnoea in lung cancer versus cardiorespiratory disease), hence targeted new therapies are difficult to develop. Historically many medications have developed clinical use within palliative care from data extrapolated from other health care settings with little empirical evidence. Though methodological challenges exist, these can be overcome allowing high-level evidence for interventions to be established. This paper will discuss some of the emerging high quality evidence that has both provided support for some interventions, and equally has demonstrated minimal net clinical benefit for others. Examples will be discussed including octreotide for bowel obstruction, ketamine for cancer pain, opioids for dyspnoea, oxygen and subcutaneous hydration. Health service intervention examples include effectiveness of integration of palliative care into routine oncological care (the example of non-small cell lung cancer) and community palliative care services.